The purpose of the proposed research is to investigate protein-DNA interactions in human chromosomes in cells from healthy and diseased individuals. The structure, arrangement, and function of chromosomal proteins will be studied by spectroscopic, biochemical, and cell biological techniques to further elucidate the role of these components in genetic control. Methods will be developed and utilized in attempts to understand the molecular bases of X chromosome inactivation and dominantly inherited conditions with increased susceptibility to neoplastic transformation.